Study of Osimertinib With and Without Ramucirumab in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria: * Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age ≥ 18 years at the time of consent. * Histologically or cytologically confirmed non-squamous, non-small cell lung cancer. * Locally advanced or metastatic disease, not amenable to curative surgery or radiotherapy. * Patients must have one of the following: * NSCLC which harbours EGFR Exon 19 deletion. * NSCLC which harbours EGFR L858R mutation. EGFR deletion/mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test (either from tissue or ctDNA from blood is allowed). If EGFR deletion/mutation testing has not been done, it should be ordered per standard of care. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix A). * Measurable disease per RECIST 1.1. * Patients with brain metastases are eligible if they are asymptomatic, are treated, or are neurologically stable for at least two weeks without the use of steroids or on stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent). These criteria must be met on day of consent. * Ability to take pills by mouth. * Previous treatment with cytotoxic chemotherapy or immunotherapy is allowed. * Patients must have adequate hematologic, coagulation, hepatic, and renal function. All laboratory tests must be obtained less than 4 w…